Diabetes and depression: The impact of this widespread disease on the brain is often overlooked

September 10, 2013, Harvard Medical School
Diabetes and depression: The impact of this widespread disease on the brain is often overlooked
Credit: iStock/jgroup

(Medical Xpress)—The complications of uncontrolled diabetes are well recognized: nerve damage, kidney disease, blindness, and circulation problems that affect the extremities. The disease's impact on the brain, however, is often overlooked. This oversight could spell trouble for millions of Americans who face the daily challenge of controlling their blood sugar.

An estimated 26 million Americans have diabetes, according to the American Diabetes Association. Another 79 million have prediabetes, a condition in which are higher than normal but not high enough for a diabetes diagnosis.

A growing body of evidence suggests that the of millions with the disease is as much at risk as are other body systems from the effects of out-of-control blood sugar.

"Unlike for certain other diseases, scientists originally didn't know where to look in the brain for the effects of diabetes," said Gail Musen, an HMS assistant professor of psychiatry and assistant investigator in the Section on Clinical, Behavioral, and Outcomes Research at Joslin Diabetes Center.

"We knew, theoretically, that because it affects so much else in the body, it also could affect the brain," she said.

Since Musen's first study of diabetes and nearly a decade ago, the scientific community has gained a greater understanding of how diabetes—primarily type 1 diabetes—affects brain function.

Shrinking brain

Musen's 2006 study, reported in the journal Diabetes, was the first comprehensive study of density changes in the brain's gray matter as a result of type 1 diabetes.

Its findings suggested that persistent hyperglycemia, or , and acute severe hypoglycemia, or , have an effect on . The gray matter reductions were small and did not necessarily show any clinically significant cognitive impairment, but the involved included the memory, attention and language processing centers.

More recently, Musen and her colleagues discovered reduced white matter integrity and cortical thickness in patients with long-standing type 1 diabetes.

"It's not clear," she said, "whether such changes to the brain will have a more profound effect as a patient ages."

Currently, Musen is using functional MRI, which measures the brain in action, to determine whether regions of the brain with gray matter density loss show impaired function.

Even though people with diabetes may show normal performance in terms of accuracy or processing speed on cognitive tasks, their brain activity may differ from that of patients without diabetes. Such changes, she said, may precede clinically relevant cognitive issues, such as memory loss an mild cognitive impairment, a precursor to Alzheimer's disease.

Another study, led by neurophysiologist Vera Novak, an HMS associate professor of medicine and a neurophysiologist at Beth Israel Deaconess Medical Center, identified a key mechanism that can lead to memory loss, depression, and other types of cognitive impairment in older adults with type 2 diabetes.

In a study published in 2011 in Diabetes Care, Novak reported that two molecules, sVCAM and sICAM, cause inflammation in the brain. Novak found that gray matter in the brain's frontal and temporal regions—areas responsible for such critical cognitive functions as decision making, verbal memory and complex task performance—were most affected.

The long-term stress and strain of diabetes management can lead to a decreased quality of life and an increased likelihood of depression. Working with colleagues at Joslin Diabetes Center, Nicolas Bolo, an HMS lecturer on psychiatry and the director of neuroimaging in psychiatry at Beth Israel Deaconess, is studying whether impaired glucose metabolism can explain the increased prevalence of depression in people with type 1 diabetes.

"It appears that chronic hyperglycemia and insulin resistance—the hallmarks of diabetes— trigger the release of these adhesion molecules and set off a cascade of events leading to the development of chronic inflammation," says Novak. "Once chronic inflammation sets in, blood vessels constrict, blood flow is reduced, and brain tissue is damaged."

Some scientists have begun calling Alzheimer's disease "type 3 diabetes" because of its characteristic complications of profound memory loss and severe cognitive decline.

Musen is cautious about this label.

"It's a good hypothesis and has generated a lot of science," she said, "but we need better studies" before drawing firm conclusions.

A chicken-or-egg question

For some time, clinicians have known that diabetes and depression often go hand in hand, but now the mechanism behind this relationship is becoming more evident. A 2010 Harvard School of Public Health study in the Archives of Internal Medicine found a biological link between the two: depression increases the risk for diabetes and diabetes increases the risk for depression.

"We've thought for a long time that the burden of type 1 diabetes is enough to increase depression," said Bolo. The long-term stress and strain of diabetes management— multiple finger sticks to check blood sugar levels, daily injections of insulin, and the worry of complications—can lead to a decreased quality of life and an increased likelihood of depression.

Working with colleagues at Joslin Diabetes Center, Bolo is studying whether impaired glucose metabolism can explain the increased prevalence of depression in people with type 1 diabetes. The team is using high-tech magnetic resonance spectroscopy to noninvasively measure metabolites in the brain.

One of these metabolites is glutamate, the principal excitatory neurotransmitter. Early results showed that brain glucose levels, as expected, are higher in people with type 1 diabetes. Glutamate is higher as well in the brains of these patients, especially in emotion centers such as the anterior cingulate cortex.

"High glucose levels in the brain increase glutamate in regions involved in emotional control, which means increased depression among people with ," said Bolo.

Bolo's research may lead to specific treatments that target the glutamate pathway in the brain and, thus, offer relief for diabetes patients suffering depression. Studies show that one such drug, ketamine, holds promise as an antidepressant that would act by blocking the action of a key protein involved in glutamate signaling in the brain. Researchers say this drug could be potentially life- saving for people with depression; unlike antidepressants such as Prozac and mood stabilizers, ketamine becomes effective in hours instead of weeks.

Although the findings of Musen, Novak and Bolo shed light on how can affect the , the standard advice for warding off complications, including cognitive decline, remains the same: control your , maintain a healthful diet, and take care of yourself.

"We know that following this advice can improve peripheral systems, like vision," said Musen, "but it can help cognition as well."

Explore further: New joint clinical trial may improve cognitive function in those with schizophrenia, diabetes

Related Stories

New joint clinical trial may improve cognitive function in those with schizophrenia, diabetes

August 30, 2013
In a joint study between Australia's University of Wollongong and China's Beijing HuiLongGuan Hospital, researchers led by Dr Mei Han have found that the prevention and treatment of diabetes might prove beneficial for people ...

Depression in diabetes patients linked to dementia, study finds

August 15, 2013
(HealthDay)—Type 2 diabetes patients who suffer depression also have more significant mental decline than those without depression, a new study finds.

Researchers identify diabetes link to cognitive impairment in older adults

November 8, 2011
Many complications of diabetes, including kidney disease, foot problems and vision problems are generally well recognized. But the disease's impact on the brain is often overlooked.

Family history of diabetes increases the risk of prediabetes by 26 percent, with effect most evident in non-obese

August 21, 2013
A study involving more than 8,000 participants has shown that people with a family history of diabetes see their risk of prediabetes increase by 26%. The research is published in Diabetologia, the journal of the European ...

Brain atrophy seen in patients with diabetes

August 23, 2013
(HealthDay)—Brain atrophy rather than cerebrovascular lesions may explain the relationship between type 2 diabetes mellitus (T2DM) and cognitive impairment, according to a study published online Aug. 12 in Diabetes Care.

Brain connectivity altered in type 2 diabetes

August 1, 2012
(HealthDay) -- Patients with type 2 diabetes mellitus (T2DM) have reduced functional connectivity in the default mode network, which is associated with insulin resistance in some brain regions, according to a study published ...

Recommended for you

Diabetes gene found that causes low and high blood sugar levels in the same family

January 15, 2018
A study of families with rare blood sugar conditions has revealed a new gene thought to be critical in the regulation of insulin, the key hormone in diabetes.

Discovery could lead to new therapies for diabetics

January 12, 2018
New research by MDI Biological Laboratory scientist Sandra Rieger, Ph.D., and her team has demonstrated that an enzyme she had previously identified as playing a role in peripheral neuropathy induced by cancer chemotherapy ...

Enzyme shown to regulate inflammation and metabolism in fat tissue

January 11, 2018
The human body has two primary kinds of fat—white fat, which stores excess calories and is associated with obesity, and brown fat, which burns calories in order to produce heat and has garnered interest as a potential means ...

Big strides made in diabetes care

January 5, 2018
(HealthDay)—This past year was a busy, productive one for diabetes research and care.

Gene therapy restores normal blood glucose levels in mice with type 1 diabetes

January 4, 2018
Type 1 diabetes is a chronic disease in which the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. A study published January 4th in Cell Stem Cell ...

Goodbye, needles? Patch might be the future for blood-sugar tracking

January 4, 2018
(HealthDay)—Developers of a new patch hope to eliminate a big barrier in type 2 diabetes treatment—painful finger-sticks and injections. The new patch—which actually uses an array of tiny needles that researchers promise ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.